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Tumor-activated lym...
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Apollonio, BenedettaKings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.;Ist Tumori Giovanni Paolo II, Dept Rare Tumors & Melanoma, Lab Tumor Immunol & Immunotherapy, Viale O Flacco 65, I-70124 Bari, Italy.
(author)
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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American Society for Clinical Investigation,2023
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-509146
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-509146URI
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https://doi.org/10.1172/JCI166070DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:153311743URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD'+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD'+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Spada, FilomenaGuys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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Petrov, NedyalkoGuys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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Cozzetto, DomenicoGuys & St Thomass NHS Fdn Trust, BRC Translat Bioinformat, London, England.;Kings Coll London, London, England.;Imperial Coll London, Fac Med, Div Digest Dis, London, England.
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Papazoglou, DespoinaKings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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Jarvis, PeterAristotle Univ Thessaloniki, Surg Dept 5, Thessaloniki, Greece.
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Kannambath, ShichinaKings Coll London, London, England.;Guys & St Thomass NHS Fdn Trust, BRC Genom Res Platform, London, England.
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Terranova-Barberio, ManuelaGuys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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Amini, Rose-MarieUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)roseamin
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Enblad, GunillaUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)gunienbl
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Graham, CharlotteKings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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Benjamin, ReubenKings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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Phillips, ElisabethKings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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Ellis, RichardGuys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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Nuamah, Rosamond
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Saqi, MansoorGuys & St Thomass NHS Fdn Trust, BRC Translat Bioinformat, London, England.;Kings Coll London, London, England.
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Calado, Dinis P.Francis Crick Inst, Immun & Canc Lab, London, England.
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Rosenquist, RichardKarolinska Institutet
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Sutton, Lesley A.Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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Salisbury, JonKings Coll Hosp NHS Fdn Trust, Dept Haematol, London, England.
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Zacharioudakis, GeorgiosAristotle Univ Thessaloniki, Surg Dept 5, Thessaloniki, Greece.
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Vardi, AnnaG Papanikolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanikolaou Hosp, HCT Unit, Thessaloniki, Greece.
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Hagner, Patrick R.Bristol Myers Squibb, Summit, NJ USA.
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Gandhi, Anita K.Bristol Myers Squibb, Summit, NJ USA.
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Bacac, MarinaRoche Innovat Ctr Zurich, Schlieren, Switzerland.
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Claus, ChristinaRoche Innovat Ctr Zurich, Schlieren, Switzerland.
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Umana, PabloRoche Innovat Ctr Zurich, Schlieren, Switzerland.
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Jarrett, Ruth F.Univ Glasgow, MRC, Ctr Virus Res, Glasgow, Scotland.
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Klein, ChristianRoche Innovat Ctr Zurich, Schlieren, Switzerland.
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Deutsch, AlexanderMed Univ Graz, Div Hematol, Graz, Austria.
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Ramsay, Alan G.Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.;Guys Canc Ctr, Lymphoma Immunol, Innovat Hub, London SE1 9RT, England.
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Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.;Ist Tumori Giovanni Paolo II, Dept Rare Tumors & Melanoma, Lab Tumor Immunol & Immunotherapy, Viale O Flacco 65, I-70124 Bari, Italy.Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
(creator_code:org_t)
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In:Journal of Clinical Investigation: American Society for Clinical Investigation133:130021-97381558-8238
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Apollonio, Bened ...
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Spada, Filomena
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Petrov, Nedyalko
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Cozzetto, Domeni ...
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Papazoglou, Desp ...
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Jarvis, Peter
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Kannambath, Shic ...
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Terranova-Barber ...
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Amini, Rose-Mari ...
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Enblad, Gunilla
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Graham, Charlott ...
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Benjamin, Reuben
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Phillips, Elisab ...
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Ellis, Richard
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Nuamah, Rosamond
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Saqi, Mansoor
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Calado, Dinis P.
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Rosenquist, Rich ...
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Sutton, Lesley A ...
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Salisbury, Jon
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Zacharioudakis, ...
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Vardi, Anna
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Hagner, Patrick ...
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Gandhi, Anita K.
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Bacac, Marina
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Claus, Christina
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Umana, Pablo
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Jarrett, Ruth F.
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Klein, Christian
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Deutsch, Alexand ...
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Ramsay, Alan G.
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